Over-the-counter medications. Most OTC remedies for insomnia contain a certain dose (around 25 mg) of the popular antihistaminic-agent diphenhydramine(Drug information on diphenhydramine) (Benadryl). Due to its deleterious effect on natural sleep's stages and its anticholinergic effects, which cause morning drowsiness and grogginess, diphenhydramine is not a good treatment for insomnia. In lab animals, at a dose slightly above what is effective therapeutically, diphenhydramine markedly affected behavior and all sleep stages (Marzanatti et al., 1989). In particular, it depressed REM and increased SWS (drowsiness). These agents are not recommended in people who use alcohol(Drug information on alcohol) and other substances, as drowsiness and grogginess might be associated with their use as well.
Melatonin, an OTC food supplement, is a brain chemical implicated in sleep regulation that has been used with mixed results and seems to be more successful among people with low endogenous (internal) levels. In 1996, Schmitz et al. suggested that melatonin(Drug information on melatonin) is decreased in alcoholics--a theory that deserves further study.
Valerian (Valeriana officinalis) is an herbal product available over the counter that improves subjective experiences of sleep when taken nightly over one- to two-week periods. It appears to be a safe sedative/hypnotic choice in patients with mild-to-moderate insomnia (Hadley and Petry, 2003). Nevertheless, no studies among substance users have been reported to date.
Prescription medications. Prescription medications for sleep disturbances have traditionally belonged to the benzodiazepine group. Their use has been controversial in the substance user, specifically the alcoholic patient (Ciraulo and Nace, 2000). In part, this is due to benzodiazepine's nonselective action at two central g-aminobutyric acid (GABA)A receptor sites: w(1) and w(2). The sedative action of benzodiazepines is related to w(1) site, whereas w(2) sites are thought to affect memory and cognitive functioning. Since alcohol is a GABA-ergic drug, these medications have a high liability for misuse, abuse and dependence by patients who are alcoholics. The ideal pharmacotherapy for this group of patients would need to be sedating, have a short half-life, possess little or no interaction with other prescriptions, have minimal or no liver metabolism, and should not induce reward, which would cause it to have low abuse potential.
A new group of benzodiazepine-like medications have been promoted as the ideal drugs due to their selective action on the w(1) subunit of the GABAA receptor. These include zolpidem(Drug information on zolpidem) (Ambien), zaleplon(Drug information on zaleplon) (Sonata) and zopiclone(Drug information on zopiclone). Unfortunately, several case reports and case series have referred to abuse of the w(1) subunit drugs. Especially at high doses, these drugs become undistinguishable from benzodiazepines (Liappas et al., 2003). In a controlled environment, one study examined the acute behavioral effects and abuse potential of three drugs commonly used to treat sleep disorders (trazodone [Desyrel], zolpidem and triazolam(Drug information on triazolam) [Halcion]) and placebo in 10 male volunteers with histories of alcohol and drug abuse (Rush et al., 1999). The measured effects of trazodone on subject-rated items and therefore abuse potential (e.g., subject ratings of "Willing to Take Again") were less than those observed with triazolam. Zolpidem and triazolam produced comparable effects on these measures. The authors suggested that trazodone has less abuse potential than triazolam and may be a viable alternative to benzodiazepine hypnotics in individuals with histories of alcohol or drug abuse. The main drawbacks of trazodone are that it causes morning drowsiness and has a one in 5,000 risk of inducing priapism, which renders it risky, considering that at least two-thirds of alcoholics in treatment are men.
Since 1998, my colleagues and I found gabapentin(Drug information on gabapentin) (Neurontin) to fit the above description of the ideal pharmacotherapy for insomnia among alcoholics and substance users (Karam-Hage and Brower, 2000). To date, we have yet to observe any abuse or subjective effects reported by patients. In 2000, we reported an open-label study of 15 successfully treated cases. Gabapentin was started at 300 mg hs, the dose was increased to response by 300 mg/day to reach a maximum of 1800 hs (average dose=900 mg) with follow-up at one month.
Antidepressant drugs with 5-HT2 blocking properties, such as mirtazapine(Drug information on mirtazapine) (Remeron) or nefazodone(Drug information on nefazodone) (Serzone), are believed to alleviate insomnia and improve sleep architecture. In patients with depression, mirtazapine produces a significant shortening of sleep-onset latency, increases total sleep time and leads to a marked improvement in sleep efficiency (Thase, 1999). No data are available on nefazodone, mirtazapine or other sedating antidepressants among substance users. My colleagues and I reported a comparison of trazodone (25 mg to 100 mg, average dose=75 mg hs) to gabapentin (300 mg to 1800 mg, average dose=1200 mg hs) (Karam-Hage and Brower, 2003). We found the latter to be significantly superior to trazodone on the overall measure and on four of the five sleep questions asked to patients. Most recently, our group conducted a double-blind, placebo-controlled study with gabapentin among alcoholics who continued to have insomnia after one week to one month of abstinencefrom alcohol (Brower et al., 2003). Gabapentin faired better than placebo not only on sleep improvement compared with baseline but it also had a direct positive effect on preventing relapse to heavy drinking, independent from its effect on sleep.
Sedating atypical antipsychotics (olanzapine [Zyprexa] and quetiapine(Drug information on quetiapine) [Seroquel]) have been suggested as alternative sleep aids for the substance user, they may be useful due to their sedative effect and impact on reducing background anxiety. Other possibilities, like newer mood-stabilizing agents with sedating qualities (e.g., topiramate(Drug information on topiramate) [Topamax]), need to be explored. Finally, experimental agents like CEE-03-310 (a selective dopamine(Drug information on dopamine) D1-like receptor antagonist in Phase II development) have demonstrated a dose-dependent enhancement of non-REM sleep at the beginning of the night without any effect on the quantity of REM sleep (Eder, 2002). These effects could be of benefit for substance users/alcoholics.